Development of new indole-derived neuroprotective agents

dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorMohareb R.M.
dc.contributor.authorAhmed H.H.
dc.contributor.authorElmegeed G.A.
dc.contributor.authorAbd-Elhalim M.M.
dc.contributor.authorShafic R.W.
dc.contributor.otherOrganic Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University of Modern Sciences and Arts (MSA)
dc.contributor.otherOctober City
dc.contributor.otherEgypt; Chemistry Department
dc.contributor.otherFaculty of Science
dc.contributor.otherCairo University
dc.contributor.otherCario
dc.contributor.otherEgypt; Hormones Department
dc.contributor.otherNational Research Centre
dc.contributor.otherDokki 12622
dc.contributor.otherCairo
dc.contributor.otherEgypt
dc.date.accessioned2020-01-25T19:58:31Z
dc.date.available2020-01-25T19:58:31Z
dc.date.issued2011
dc.descriptionScopus
dc.description.abstractThere is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. The present study aimed at synthesizing new functionalized indole derivatives with structures justifying neuroprotective activity using l-tryptophan (TRP)� as starting material. The potential neuroprotective effect of these newly synthesized agents against acrylamide (ACR) induced neurotoxicity was investigated in adult female rats. The novel indole derivatives, indolylmethyl pyridine derivatives 9a,b, pyrimidinylindolyl propanone derivatives 12a-c, pyrazolylindolyl propanone derivatives 14a,b, and indolyl tetrazolopropanoic acid derivative 17 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [ip, 50 mg kg -1 body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with the indole derivatives 9b, 12c, 14a, and 17 (ip, 50 mg kg-1 b. wt.) prior to ACR produced neuroprotective activity with various intensities depending on the structure of each compound. Compound 17 in which the tetrazole ring was attached to the TRP moiety ranked as the strongest neuroprotective agent. All the tested compounds have been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by ACR administration. � 2011 Elsevier Ltd. All rights reserved.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=25786&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1016/j.bmc.2011.03.031
dc.identifier.doiPubMed ID 21493072
dc.identifier.issn9680896
dc.identifier.otherhttps://doi.org/10.1016/j.bmc.2011.03.031
dc.identifier.otherPubMed ID 21493072
dc.identifier.urihttps://t.ly/GJPrk
dc.language.isoEnglishen_US
dc.relation.ispartofseriesBioorganic and Medicinal Chemistry
dc.relation.ispartofseries19
dc.subjectIndoleen_US
dc.subjectNeuroprotectiveen_US
dc.subjectPyrazoleen_US
dc.subjectPyridineen_US
dc.subjectPyrimidineen_US
dc.subjectTetrazoleen_US
dc.subjectTryptophanen_US
dc.subject1 (3,5 diamino 4,5 dihydro 1 phenylpyrazol 4 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 oneen_US
dc.subject1 (3,5 diamino 4,5 dihydro 1h pyrazol 4 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 oneen_US
dc.subject1 (4,6 diamino 2 imino 5h pyrimidin 5 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 oneen_US
dc.subject1 (4,6 diamino 2 oxo 5h pyrimidin 5 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 oneen_US
dc.subject1 (4,6 diamino 2 thioxo 5h pyrimidin 5 yl) 3 (1h indol 3 yl) 2 (methylenamino)propan 1 oneen_US
dc.subject2 (1h tetrazole 5 methylencarboxamido) 3 (1h indol 3 yl)propanoic aciden_US
dc.subject2 [(1h indol 3 yl)methyl] 5 amino 3 (phenylamino)pyridine 4 carbonitrileen_US
dc.subject2 cyano 5 (1h indol 3 yl) 4 (methylenamino) 3 oxopentanonitrileen_US
dc.subject3 (1h indol 3 yl) 2 (methylenamino) n phenylpropanamideen_US
dc.subject3 (1h indol 3 yl) 2 (methylenamino)propanoic aciden_US
dc.subject3 (1h indol 3 yl) 2 (methylenamino)propanoyl chlorideen_US
dc.subjectacrylamideen_US
dc.subjectethyl 2 [(1h indol 3 yl)methyl] 5 amino 3 (phenylamino)pyridine 4 carboxylateen_US
dc.subjectindole derivativeen_US
dc.subjectindolylmethylpyridine derivativeen_US
dc.subjectlactate dehydrogenaseen_US
dc.subjectmalonaldehydeen_US
dc.subjectpyrazolylindoylmethylenaminopropan 1 one derivativeen_US
dc.subjectpyrimidinylindolylmethylenamino propan 1 one derivativeen_US
dc.subjectunclassified drugen_US
dc.subjectanimal experimenten_US
dc.subjectanimal modelen_US
dc.subjectanimal tissueen_US
dc.subjectantioxidant activityen_US
dc.subjectarticleen_US
dc.subjectcarbon nuclear magnetic resonanceen_US
dc.subjectcontrolled studyen_US
dc.subjectcrystallizationen_US
dc.subjectdrug efficacyen_US
dc.subjectdrug structureen_US
dc.subjectdrug synthesisen_US
dc.subjectenzyme activityen_US
dc.subjectfemaleen_US
dc.subjectglutathione metabolismen_US
dc.subjectlipid peroxidationen_US
dc.subjectneuroprotectionen_US
dc.subjectneurotoxicityen_US
dc.subjectneurotransmissionen_US
dc.subjectnonhumanen_US
dc.subjectoxidative stressen_US
dc.subjectproton nuclear magnetic resonanceen_US
dc.subjectraten_US
dc.subjectroom temperatureen_US
dc.subjectAnimalsen_US
dc.subjectBrainen_US
dc.subjectFemaleen_US
dc.subjectGlutathioneen_US
dc.subjectGlutathione Peroxidaseen_US
dc.subjectIndolesen_US
dc.subjectLactate Dehydrogenasesen_US
dc.subjectMalondialdehydeen_US
dc.subjectNeuroprotective Agentsen_US
dc.subjectPropionic Acidsen_US
dc.subjectRatsen_US
dc.subjectRats, Sprague-Dawleyen_US
dc.subjectSuperoxide Dismutaseen_US
dc.subjectRattusen_US
dc.titleDevelopment of new indole-derived neuroprotective agentsen_US
dc.typeArticleen_US
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